College of Pharmacy, Hubei University of Chinese Medicine, Wuhan, Hubei, 430065, China.
College of Basic Medicine, Hubei University of Chinese Medicine, Wuhan, Hubei, 430065, China.
Anal Biochem. 2022 Sep 15;653:114774. doi: 10.1016/j.ab.2022.114774. Epub 2022 Jun 8.
For many years, Shiliu Buxue Syrup (SLBXS) has been used in the treatment of anemia in Xinjiang, China. However, the potential therapeutic mechanism of SLBXS in the treatment of anemia remains unclear. We qualitatively analyzed the ingredients of SLBXS and predicted the underlying mechanisms by network pharmacology. A mice model of anemia was established by subcutaneous injection of 1-Acetyl-2-phenylhydrazine (APH). Spleen metabolomics was performed to screen potential biomarkers and pathways related to anemia. Furthermore, core targets of crucial pathways were experimentally validated. Finally, molecular docking was used for predicting interactions between compositions and targets. Network pharmacology indicated that the 230 SLBXS ingredients may affect 141 target proteins to regulate the PI3K/AKT and HIF-1 signaling pathways. Metabolomics revealed that SLBXS could mediate 30 biomarkers, such as phosphoric acid, l-pyroglutamic acid, alpha-Tocopherol, 1-stearoyl-rac-glycerol, and dihydroxyacetone phosphate, to regulate drug metabolism-other enzymes, glutathione metabolism, glycolysis or gluconeogenesis, nicotinate and nicotinamide metabolism, nitrogen metabolism, and purine metabolism. Western blot indicated that SLBXS can regulate the protein expression levels of AKT1, Bcl2, Caspase3, HIF-1α, VEGF-A, and NOS2. The molecular docking revealed that most of the compositions had a good binding ability to the core targets. Based on these findings, we speculate that SLBXS treats anemia mainly by modulating the PI3K/AKT and HIF-1 pathways and glutathione and glycolytic metabolisms.
多年来，石榴补血口服液（SLBXS）一直用于治疗中国新疆的贫血症。然而，SLBXS 治疗贫血的潜在治疗机制尚不清楚。我们通过网络药理学定性分析了 SLBXS 的成分，并预测了其潜在的作用机制。通过皮下注射 1-乙酰基-2-苯基肼（APH）建立贫血小鼠模型。进行脾脏代谢组学以筛选与贫血相关的潜在生物标志物和途径。此外，还对关键途径的核心靶标进行了实验验证。最后，分子对接用于预测成分与靶标之间的相互作用。网络药理学表明，SLBXS 的 230 种成分可能通过影响 141 个靶蛋白来调节 PI3K/AKT 和 HIF-1 信号通路。代谢组学揭示，SLBXS 可以调节 30 种生物标志物，如磷酸、L-焦谷氨酸、α-生育酚、1-硬脂酰基-rac-甘油、二羟丙酮磷酸等，来调节药物代谢-其他酶、谷胱甘肽代谢、糖酵解或糖异生、烟酰胺和烟酸代谢、氮代谢和嘌呤代谢。Western blot 表明，SLBXS 可以调节 AKT1、Bcl2、Caspase3、HIF-1α、VEGF-A 和 NOS2 的蛋白表达水平。分子对接表明，大多数成分与核心靶标具有良好的结合能力。基于这些发现，我们推测 SLBXS 主要通过调节 PI3K/AKT 和 HIF-1 途径以及谷胱甘肽和糖酵解代谢来治疗贫血。
